Application of Mesoporous Silica Foam for Immobilization of Salen Complexes in Chiral Intermediates Synthesis

Article abstract of DOI:10.1002/bkcs.10271

A route to synthesize porous materials with a hierarchical micro/meso/macroscopic pore system was investigated. Meso/macroporous monolithic silica foams with a large pore size could be fabricated from a mixture of monodispersed PMMA beads and SBA-15, -16 sol solutions. The size, bulk shape and density of the mesoporous monolithic foam could be controlled by the container and the heat treatment temperature. Drying at temperatures higher than 300°C resulted in an expansion of the SBA silica sol and its solidification to form the mesoporous foams. In contrast, only a dense silica monolith was obtained after full evaporation of the solvent at room temperature without releasing the foam structure in the monolithic body. A large fraction of macroporosity in three dimensions was formed in the monolith body, and the remaining silica walls exhibited uniform mesoporosity. Hydrolytic and phenolic ring-opening of epoxides were performed successfully using chiral (salen)Co-BF₃ complex-immobilized catalysts in the packed bed of a continuous flow system. Very high catalytic activity with desirable enantioselectivity was obtained in asymmetric catalysis.

Full text of DOI:10.1002/bkcs.10271

Article
DOI: 10.1002/bkcs.10271
BULLETIN OF THE
H.-G. Jeon et al.
KOREAN CHEMICAL SOCIETY
Application of Mesoporous Silica Foam for Immobilization of Salen
Complexes in Chiral Intermediates Synthesis
Hoon-Gi Jeon, Seong Dae Choi, Sang Kwon Jeon, Geun Woo Park,
*
Jin Young Yang, and Geon-Joong Kim
Department of Chemical Engineering, Inha University, Incheon 402-751, Korea. *E-mail: kimgj@inha.ac.kr
Received November 22, 2014, Accepted January 12, 2015, Published online April 24, 2015
A route to synthesize porous materials with a hierarchical micro/meso/macroscopic pore system was investi-
gated. Meso/macroporous monolithic silica foams with a large pore size could be fabricated from a mixture of
monodispersed PMMA beads and SBA-15, -16 sol solutions. The size, bulk shape and density of the meso-
porous monolithic foam could be controlled by the container and the heat treatment temperature. Drying at
temperatures higher than 300 °C resulted in an expansion of the SBA silica sol and its solidification to form
the mesoporous foams. In contrast, only a dense silica monolith was obtained after full evaporation of the sol-
vent at room temperature without releasing the foam structure in the monolithic body. A large fraction
ofmacroporosityinthreedimensionswasformedinthemonolithbody, andtheremainingsilicawallsexhibited
uniform mesoporosity. Hydrolytic and phenolic ring-opening of epoxides were performed successfully
using chiral (salen)Co-BF3 complex-immobilized catalysts in the packed bed of a continuous flow system.
Very high catalytic activity with desirable enantioselectivity was obtained in asymmetric catalysis.
Keywords: Monolith, Mesoporous silica, Foam, SBA-16, Enantioselectivity
Introduction
physicochemical properties ofthese materials can beexpected
if crystalline zeolites can be incorporated into the mesoporous
frameworks.
Microporous zeolitic materials with pore diameters less than
1.0 nm have attracted considerable interest in the field of
adsorption and catalysis owing to their high surface area,
unique pore structure and hydrothermal stability.1–3 However,
their pore sizes are not efficient for processes involving large
molecules. Consequently, some recent research on the synthe-
sis of mesoporous materials with large pore sizes and uniform
pore size distribution has been conducted.4–11 Nano-
structured porous materials continue to attract significant
research interest and have had a great impact in many applica-
tions, including catalysis, sorption, and separation.12 Meso-
porous materials with a pore diameter in the range of
2–10 nm may be suitable for a wide range of applications in
enantioselective catalytic reactions to synthesize valuable
medical substances.13–16 The large surface areas of porous
materials can be used efficiently to anchor the active metal
complexes of a large size through covalent bonding, and the
large mesopore channels may allow the easy diffusion of reac-
tants to these active sites for catalysis. The formation of poros-
ity on two or three different length scales in an ordered manner
with interconnectivity between the pores and with a hierarchi-
cal structure would be advantageous for a variety of applica-
tions. For catalytic applications, reactant molecules need
to access readily the interior pore structure. Hierarchical
materials containing both interconnected macroporous and
mesoporous structures have enhanced properties compared
to single-sized pore materials due to increased mass transport
through the pore channels with a high specific surface area on
the molecular levels. Obviously, significant advances in the
Many researches were focused on the production of opti-
cally pure products due the increasing demand of such drugs
to be administered in an optically pure form. The syntheses of
optically pure chemicals have significant potential. Terminal
epoxides are one of the important subclasses for organic syn-
thesis. As a consequence, the preparation of optically pure ter-
minal epoxideshasbeenasignificanttarget forthesynthesisof
chiral building-block in the pharmaceutical industry. The cat-
alytic ringopening reaction providesa practical manner topre-
pare stereo chemically-enriched terminal epoxides. Several
systems based on the chiral cobalt–salen complexes are quite
efficient in the highly enantioselective synthesis of chiral
epoxides by hydrolytic kinetic resolution (HKR). Typically,
HKR of racemic terminal epoxides with water catalyzed by
a chiral Co(III) salen complex may provide highly enantio-
riched epoxides and 1,2-diols. A recent study reported that
[Co(salen)]-type complexes bearing transition-metal salts or
BF3 exhibited good enantioselectivity and reactivity for the
HKR of racemic terminal oxiranes in the synthesis of chiral
atenolol.17 From a practical synthetic point of view, phenol
derivatives are appealing candidates as nucleophiles for the
ring opening of racemic ( )-ephichlorohydrine (( )ECH) pro-
viding direct access to enantiopure α-aryloxy alcohols using
chiral cobalt–salen complexes.18,19 These recently developed
salen-based catalysts are appealing candidates for the attach-
ment of homogeneous chiral salen ligands to the inorganic
supports, and the corresponding immobilized salen deriva-
tives have been shown to be efficient for the phenolic kinetic
Bull. Korean Chem. Soc. 2015, Vol. 36, 1396–1404
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Application of Mesoporous Silica Foam in Chiral Intermediates Synthesis
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resolution (PKR) of terminal epoxides.20 Heterogeneous cat-
alysts offer the practical advantages of the facile separation
from reactants and products, as well as recovery and reuse.
Considerable effort has been devoted not only to the develop-
ment of active catalysts but also to finding ways to enable
repeated use.21–24 This is particularly important for chiral cata-
lysts, which arenormallymoreexpensive than achiral catalysts.
These recently developed chiral salen-based catalysts are
appealing candidates for the development of new methods
for the recycling of chiral catalysts. Therefore, the present study
focused on the development of optically active catalysts desir-
able for repeated use without any treatment after the reaction.
In this study, a mesoporous monolithic silica foam was
newly fabricated from SBA sols. A large meso/macroporous
silica monolith with the shape of the mold was synthesized
on the centimeter scale. The foam-type silica monolith compo-
siteswiththree-dimensionalmacroporechannelsalsocouldbe
obtained from a mixture of polymethylmetacrylate/SBA
(PMMA/SBA) silica sol. The PMMA/SBA silica sol was
expanded and solidified to a foam structure at high tempera-
tures. After removing the PMMA polymer beads, a mesopor-
ous silica foam remained. Large fractions of macroporosity in
three dimensions were formed in the monolith body, and the
remaining silica walls exhibited uniform mesoporosity. The
micro/meso/macroporous silica monolith could be also fabri-
cated from the MFI zeolite/SBA sol mixture by expansion into
a foam structure. These porous supports were used to anchor
the (BF3) containing chiral Co(III) salens, and they were
packed in the tube for use as a catalyst in the continuous flow
typepackedbedreactorsystem. Theasymmetriccatalyticactiv-
itiesofthesecatalystswereinvestigatedintheHKR andPKRof
ECH. This hierarchically-ordered macro/mesoporous silica
was quite useful for anchoring bulky chiral catalysts, such as
salencomplexes. BasedontheasymmetricHKRandPKRreac-
tions performed in this study, the meso/macroporous silica
monolithic foams can be applied as effective supports for the
enantioselective synthesis of chiral compounds.
Experimental
Materials Synthesis. The synthesis of mesoporous silica
foam was performed basically using a silica sol containing a
surfactant in ethanol (EtOH) solvent. Before the foaming step
at high temperatures, PMMA spheres or zeolite powders were
added to the as-synthesized SBA-16 sol. First, the calculated
amount of (ethylene oxide)106–(propylene oxide)70–(ethylene
oxide)106 (Pluronic F-127, numbers in subscripts denote the
molar ratios of each component, Aldrich) was dissolved in
EtOH. To prepare the prehydrolyzedinorganicprecursor solu-
tion, tetraethoxy orthosilicate (TEOS, Aldrich) dissolved in
EtOH was hydrolyzed in an aqueous hydrochloric acid
(HCl) solution. The TEOS:F-127:ethanol:water:HCl molar
ratio was 1:0.011:10.1:12:0.24. This SBA-16 sol was concen-
trated by evaporating the solvent until the volume of the sol
mixture was reduced to one-third compared with the starting
volume. At this time, PMMA spheres or MFI zeolite powders
were added to the viscous silica sol-solution. The monodis-
perse PMMA spheres with mean diameters of 30 μm
(TAFTIC TM FH-S series; for use of Light diffuser) were pur-
chased from Toyobo Co. MFI type zeolite was treated with a
diluted HF solution to produce mesopores in the microporous
crystals. Theresulting mixturewasstirred atroom temperature
and then kept at 300 ꢀC to allow self-expansion during solid-
ification of the sol into the gel foam. Scheme 1 presents the
HF-treated Mesoporous
Zeolite powder
Polymer
Bead
Calcination
Gelation to make
Mesoporous Silica
Foam at 300°C
Evaporation
To 1/3 volume
SBA-16 sol
Preparation
Scheme 1. Procedure for the fabrication of monolithic mesoporous silica foams.
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Application of Mesoporous Silica Foam in Chiral Intermediates Synthesis
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typical procedure to fabricate the mesoporous silica foam. The
PMMA spheres and F-127 surfactant in the silica foam were
removed bydirect calcination at 600 ꢀC for4 hin air. Theheat-
ing rate was maintained 1 ꢀC/min. In addition, a SBA-15 sol
was also prepared using P-123 (Aldrich, 98%) as a surfactant.
Immobilization of Chiral Salen Catalyst on Bimodal
Porous Materials. Anhydrous aluminum chloride (Aldrich,
98%) was dissolved in dried methanol. The monolithic silica
foam was added to that solution. The aluminum chloride load-
ings used were 10, 20, and 30 wt% (Al basis) compared with
the silica support. The solvent was evaporated and the recov-
ered solid sample was calcined at 600 ꢀC for 3 h in air.
For the synthesis of chiral Co(III)-(BF3) salen, (R,R)-(−)-N,
N0-bis(3,5-di-tert-butyl-salicylidene)-1,2-cyclo-hexane dia-
mino cobalt (II) (Aldrich, 98%) was oxidized in air for 4 h
in the presence of methylene chloride (MC) and BF3ꢁ2H2O
(Co(II) salen:BF3ꢁ2H2O mole ratio = 1:1) at room tempera-
ture. The mixture was concentrated to dryness. Scheme 2 pre-
sents the immobilization method to obtain the catalyst and
photographs of the silica foams for the fresh and catalyst
loaded foams. The heterogenized chiral Co salen catalysts
were packed in a stainless steel column (inner diameter 2 cm ×
length 15 cm), and this fixed bed type reactor was adopted
to examine the catalytic activities in the HKR and PKR reac-
tion of terminal epoxides. The reactants were circulated by
a pump, and the inside pressure could be controlled up to
20 atm. In a representative reaction of ( )ECH (Aldrich,
98%) and phenol, a mixture of tert-butyl methyl ether
(TBME; 150 ml, Aldrich) as a solvent, ( )ECH (9 g) and phe-
nol (4.2 g) were circulated by pump through the reactor bed
packed with the salen immobilized catalyst (3.4 g) at room
temperature. The conversion and enantiomeric excess per-
centage (ee%) values were determined by GC using the chiral
capillary columns (CHIRALDEX [G-TA] and [A-TA] col-
umns, 20 m × 0.32 mm i.d., Astech, USA).
Characterization of Materials. The mesostructures of the
inorganic composites were characterized by X-ray diffraction
(XRD; DMAX 2500, Rigaku, Tokyo, Japan). In addition,
transmission electron microscopy (TEM; Phillips CM-220,
The Netherlands) was performed to examine the pore struc-
tures of the purely mesoporous or meso/macroporous materi-
als. The morphologies of the samples were examined by
scanning electron microscopy (SEM; S-4200, Hitachi, Japan).
The N2 adsorption and desorption isotherms were determined
on a Micrometrics sorptometer (ASAP 2000, Micrometrics,
Norcross, GA, USA) at −196 ꢀC. The samples were outgassed
under 10−5 torr at 200 ꢀC prior to the measurement. The parti-
cle size distributions of the original polymer beads were deter-
mined by SEM.
Results and Discussion
The centimeter-scale mesoporous monolithic silica foam
could be fabricated using SBA-15 or SBA-16 sol, which
was obtained from a pure SBA sol or in conjunction with
PMMA beads and Zeolite powder to control the bulk shape
and macropore structure. Figure 1 shows a SEM image of
the PMMA beads used as a template. The silica sol hydrolyzed
in the presence of Pluronic F-127 (for SBA-16) was mixed
with the template polymer spheres or MFI zeolite during heat
HKR
Reaction
In Fixed bed
Reactor
Impregnation
of Chiral Salen
Complexes
Catalyst
Loading
Scheme 2. Immobilization of chiral Co salen catalyst on the support and packing in the tube reactor for use in the continuous flow type reaction
system.
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Application of Mesoporous Silica Foam in Chiral Intermediates Synthesis
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treatment for foaming. After complete drying and removal of
the polymer beads by calcination, the macro/mesoporous sil-
ica materials were fabricated with macroporous channels of
different sizes inside the sample, depending on the amount
of PMMA template added. For fabrication of the micro/
meso/macroporous silica monolith foam, a mixture of fresh
H-type MFI zeolite powder and SBA sol was expanded and
solidified into a foam structure. In this study, however, the
HF treated mesoporous MFI zeolite was incorporated to
increase the mesoporosity in the resulting silica foam. The
formation of mesopores in MFI zeolite was confirmed by
TEM (Figure 1(e)) and BET analysis (Figure 1(f )).
The size, density, and bulk shape of the mesoporous mon-
olithic foam could be controlled, according to the container
and the heat treatment temperature (Figure 2). At high drying
temperatures, e.g., 300 ꢀC, the SBA silica sol was expanded
and solidified to make the mesoporous foams. In contrast,
the dense silica monolith was obtained after full evaporation
of the solvent at room temperature. In this case, no foam struc-
ture was found in the monolithic body. Figure 2 shows the
(a)
(b)
(c)
180
(f)
(d)
(e)
170
160
150
140
130
120
110
0.0
0.2
0.4
0.6
0.8
1.0
P/P
0
Figure1. SEMimagesof30 μmPMMAbeads(a), freshMFIzeolite(b), HFtreatedmesoporousMFIzeolite(c)usedasadditives. TEMimageof
fresh MFI zeolite (d), HF-treated MFI zeolite (e), and BET result for HF treated MFI zeolite (f ).
(a)
(b)
(e)
(c)
(d)
Figure 2. Photographs of the mesoporous silica foams: (a) left: pure SBA-16 foam; middle: MFI zeolite added one; right: PMMA bead added
one; (b) fresh mesoporous SBA-16 foam, and (c) chiral salen complex anchored SBA-16 foam, (d) the sample (c) in MC solvent for the leaching
test, and (e) fixed bed-type reaction system.
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Application of Mesoporous Silica Foam in Chiral Intermediates Synthesis
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shape of the calcined silica monolith foam made by replicating
theshape oftubemold. Thecylindricalshape ofthesilicamon-
olith was obtained on the centimeter-scale (Figure 2(a)).
After immobilization of the chiral salen complexes with a
BF3 group on the Al-doped silica foam support, the color of
the support turned to black indicating that they had been
anchored (Figure 2(c)). The homogeneous salen catalyst
adhered strongly to the support surfaces after the washing of
the physically adsorbed complexes, without extraction in
the organic polar solvents (Figure 2(d)). These heterogeneous
chiral Co(III)-(BF3) salen catalysts were packed in the tube
reactor for use in the continuous flow type packed bed reactor
system. Figure 2(e) shows the fixed bed reaction system used
in this study.
Figure 3 presents the cross-sectional SEM images of silica
monoliths obtained from the SBA-16 sol and monodispersed
PMMA spheres. After calcination, the incorporated PMMA
polymer beads were burned out and solid mesoporous silica
remained. The large fractions of macroporosity in three dimen-
sions were observed for the meso/macro composite fabricated
from the PMMA/SBA-16 sol mixture (Figure 3(a)). When a
large amount of PMMA was introduced, the remaining silica
walls exhibited uniform mesoporosity, interconnected through
windows, whose vacant void portion typically had the same
shape as the starting PMMA template (Figure 3(b)). Figure 3
shows the similar form shapes of the silica monolith compo-
sites. Those samples displayed interconnected three-
dimensional macropore channels. When the silica sol and
MFI zeolite were mixed, they were also expanded into the form
structure and combined (Figure 3(d)).
The presence of mesopores in the silica foams was con-
firmed by XRD, TEM, and N2 adsorption analysis. A TEM
image of the monolith sample shown in Figure 4 showed a
three-dimensional hexagonal array of pore structures for the
silica foam synthesized from the SBA-15 sol containing the
P-123 surfactant. However, a disordered mesopore structure
was observed for the calcined silica foam sample synthesized
from the SBA-16 sol but the mesoporosity throughout the
whole silica foams was observed.
Figure 5 shows the XRD patterns of meso/macroporous
SBA-15 and SBA-16 made by a sol–gel process. In the
XRD pattern, SBA-16 sample shows an intense diffraction
peak for the (1 0 0) plane. This might be due to the formation
ofadisorderedporestructure. InFigure5(b), anintensepeakat
1.2ꢀ (2θ) was observed with weak peaks in the 2θ region
between 1.82ꢀ and 2.4ꢀ, which corresponded to the (1 0 0)
main peak intensity and the overlap of two (1 1 0) and
(2 0 0) peaks. This is typical for a SBA-15 mesostructure
showing regular hexagonal pore channels. These XRD pat-
terns correspond well to the results obtained by TEM, as
shown in Figure 4.
Figure 6 shows the N2 adsorption-desorption isotherms of
calcined SBA-15 and -16 mesoporous silica foam; the pore
size distribution is plotted in the inset. The N2 adsorption–
desorption isotherm of the calcined original SBA-15 showed
significant changes with pressure, which is an indication of the
presence of mesoporosity (Figure 6(a)). In contrast, as it is
shown in Figure 6(b), the SBA-16 mesoporous foam sample
showed hysteresis due to the cage-like mesopore channels
with an ink-bottle neck.
(a)
(b)
(d)
(c)
Figure 3. SEM images of silica foams at low magnification: (a, b) foams from PMMA/SBA-16 sol (60 wt% PMMA), (c) pure SBA-16 foam, and
(d) foam obtained from the MFI/SBA-16 sol mixture.
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(a)
(b)
Figure 4. TEM images of the mesoporous silica foams: (a) mesoporous SBA-15 and (b) mesoporous SBA-16 foam.
and they were packed in the tube for use as a catalyst. The
(a) SBA-16 foam by sol-gel process
(b) SBA-15 foam by sol-gel process
trends in the activity and enantioselectivity of the Co(III)-
(BF3) salens immobilized on mesoporous silica foam were
examined for the HKR and PKR reaction of ECH in the con-
tinuous flow type packed bed reactor system. Figure 8 shows
the activities of the catalyst in the asymmetric HKR of ECH by
water in the circulating flow type packed-bed reactor. The
results show the change in ee% of the resolved ECH with
the reaction time. The HKR of ( )ECH was particularly effi-
cient in terms of both the enantioselectivity (ee% up to 98%)
and fast reaction rate. The reaction rate in asymmetric catalysis
decreased with increasing flow rates of the reactants through
the packed reactor. The high loading of the salen catalyst on
the support exhibited higher activity, but a dilution of the reac-
tants by a large amount of solvent resulted in a low reaction
rate. For the effect of aluminum (Al) contents in SBA support,
higher reaction rates were observed, when the increasing con-
centration of active sites was allowed on the same amount
of supports. The active site means the chiral Co(III)-(BF3)
salen complex itself attached on the support. However the
anchored amount of homogeneous salen complex was propor-
tional to the contents of Al present on the supports, as shown in
Scheme 2. 25 Aluminum chloride has oxidized during a heat
treatment in air, and the Lewis acids generated by alumina
oxide could combine the salen complexes strongly on the sup-
port. Ahigher localpopulation ofsalen complexes onthesame
surface area waseffective toaccelerate thereaction rates andto
increase the enantioselectivity.19 It is noteworthy to mention
that Al showed no catalytic activity in this asymmetric reac-
tion. The fixed bed-type insoluble heterogeneous Co(III)-
(BF3) salen catalysts could be applied easily in asymmetric
catalysis with high efficiency.
(b)
(a)
2
4
6
2 Theta (degree)
Figure 5. XRD patterns of the calcined silica foams fabricated from
the SBA-15 and SBA-16 sol solution.
The heterogenized chiral Co–salen complexes present on
the surfaces of mesoporous SBA-16 were characterized by
FT-IR spectroscopy (Figure 7). SBA-16 can supply sufficient
vacant spaces to attach the very large (salen) complexes inside
the pore spaces. The characteristic IR peaks for homogeneous
salen were observed at 1535–1612 and 2958–2950 cm−1 on
the spectra. The peaks near 2950 cm−1 are due to the absorption
by two aromatic rings and 1535–1612 cm−1 due to aliphatics
such as cyclohexane and tert-butyl groups in the
salen structure (Figure 7(a)). On the spectrum (B), the symmet-
ric and asymmetric stretching vibration bands for SiO2 of SBA-
16 are found at 1000 and 1100 cm−1. However, the broad band
near 3500 cm−1 is for the absorption due to the water molecules
or silanol OH groups present on the mesoporous support. The
chiral (salen) cobalt (III) complex-anchored mesoporous SBA-
16 (Figure 7(c)) showed similar absorption bands of the pure
homogeneous chiral (salen) complex (Figure 7(a)).
The PKR reaction of ( )ECH by phenol was performed in
the fixed bed reaction system and the results of the catalytic
activity are summarized in Figure 9. As shown in this result,
relatively highconversionwasobtained usingthecatalystwith
a high aluminum chloride loading under the same reaction
conditions. In addition, the ee% of epoxide increased at a high
aluminumchlorideloadingforthesamereactiontimeandflow
The micro/meso/macroporous silica forms were used as a
support to anchor the (BF3) containing chiral Co(III) salens,
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OH
O
O
OH
400
350
300
250
200
150
100
50
+
H2O
+
Salen Catalyst
room temp.
Cl
Cl
(a)
R
_
+
(
)
1.0
0.55
equiv.
equiv.
100
200
150
100
50
80
60
40
20
0
0
-50
0
50 100 150 200 250 300
Pore Diameter(A)
monolith of SBA-15
BET surface area;
Average pore diameter; 46.6 A
511.3 m2/g
50ml/min; 30wt% AlCl3
50ml/min; 20wt% AlCl3
50ml/min; 10wt% AlCl3
80ml/min; 30wt% AlCl3
0.0
0.2
0.4
0.6
0.8
1.0
P/P0
350
300
250
200
150
100
50
0
2
4
6
8
10
12
Time (h)
(b)
Figure 8. Catalytic activities in the HKR of racemic ECH under dif-
ferent catalyst loadings and flow rates (THF solvent).
0.6
0.5
0.4
0.3
0.2
0.1
0.0
O
Cl
OH
OH
O
Catalyst
solvent
+
Cl
_+
(
)
10 15 20 25 30 35 40 45 50 55
Pore Diameter (Å)
100
90
80
70
60
50
40
30
20
10
0
SBA-16made by sol-gel process
BET surface area ;
470.1 m2/g
Average pore diameter; 41.6 A
0.0
0.2
0.4
0.6
0.8
1.0
P/P0
Figure 6. N2 adsorption–desorption isotherms: (a) calcined SBA-15
and (b) SBA-16 foam.
30wt% AlCl3
20wt% AlCl3
10wt% AlCl3
(a)
0
2
4
6
8
10
12
14
16
18
Time (h)
Figure 9. ee% change in ECH on the Co(III)-(BF3) salen catalysts
immobilized on mesoporous silica foam in the asymmetric PKR with
phenol (flow rate: 50 mL/min, TBME solvent).
(b)
(c)
rate. The increase in ee% for the reactant ECH indicates that
one optical epoxide was attacked selectively by nucleophile
phenol on the chiral salen catalyst. Based on the observed
results, a high loading of salen complexes on the support is
essential to promote the reaction in terms of high enantioselec-
tivity and conversion.
1000
2000
3000
4000
Wave number(cm-1)
Figure 7. FT-IR spectra for: (a) homogeneous (BF3) containing Co
salen complex, (b) calcined SBA-16 foam, and (c) Co salen-
immobilized SBA-16 foam.
Table 1 lists the conversion and enantioselectivity obtained
using different substrates with the catalyst and a 30 wt% AlCl3
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Table 1. PKR reaction of terminal epoxides to diols on the Co(III)-
(BF3) salens immobilized over meso/macroporous foam composites
(the product yield is based on the reactant phenol derivatives).
O
Cl
OH
OH
O
Catalyst
solvent
+
Cl
_
+
( )
O
Cl
OH
OH
O
100
90
80
70
60
50
40
30
20
10
0
Catalyst
solvent
+
Cl
+_
( )
R
R
Substrate
(R)
Time
(h)
Yield of
product (%)
ee% of
product
Entry
1
2
3
H
Cl
CH3
7
10
11
84
76
82
98
96
98
1st cycle
2nd cycle
3rd cycle
loading, which was used to anchor the salen complexes onto
the support. Both the electron-poor or -rich phenols reacted
with ( )ECH enantioselectively to provide the corresponding
α-aryloxy alcohols in good yield and high ee%. The introduc-
tion of Co(III)-(BF3) salens in the meso/macroporous support
was an essential factor for enhancing the catalytic activity and
enantioselectivity. These salen-based catalysts showed a
unique catalytic property to accelerate the kinetic resolutions
in a highly efficient manner. No reaction has proceeded in the
absence of the salen complexes.
0
2
4
6
8
10
12
14
16
18
Time (h)
Figure 10. Catalytic activity of 30 wt% AlCl3-loaded chiral salen cat-
alyst in recycle reaction (flow rate: 50 mL/min, TBME solvent).
The recyclability of the catalysts was examined in a PKR of
( )ECH using the 30 wt% Al-loaded heterogeneous catalyst.
The catalyst was reused by simple washing with MC and THF
after thereaction. Thecatalytic activity decreased slightly after
3 times reuse, indicating that some leaching of the salen cata-
lyst from the support occurred during the reaction, as shown in
Figure 10. No chemical isolation step of the salen catalyst was
needed from the product solution in the heterogenized catalyst
system.
The solvent plays a crucial role in this reaction. In the
typical example, during the PKR reaction of ( )ECH with
phenol or chlorophenol, the effects of polar and nonpolar sol-
vents were examined, and nonpolar solvents, such as TBME
was found to be the most suitable solvent, as illustrated in
Figure 11.
Chlorophenol
Phenol
The results obtained in this study highlight the importance
to the asymmetric ring-opening of ( )ECH by HKR or PKR
in pharmaceutical synthesis because the highly enantio-
enriched β-blockers can be synthesized easily in high yield
using chiral cobalt-salen-type complexes. Further transfor-
mation into (S)-atenolol was accomplished using well-known
simple methods (i.e., by the addition of excess iPrNH2 in the
presence of H2O at the reflux temperature, followed by treat-
ment with aqueous NH4OH). The heterogeneous catalyst
could be recycled successfully without significant loss of
activity and it is easy to isolate the immobilized salen cata-
lysts from the product containing epoxide and α-aryloxy
alcohols.
Figure 11. Effect of various solvents on the enantioselectivity in the
PKRreactionofECHbyphenolandchlorophenol(highestee%inthe
system, flow rate: 40 mL/min).
Conclusion
Porous materials with bimodal pore structures were synthe-
sized, and their pore system was characterized by instrumental
analysis and by comparing the catalytic activity at room tem-
perature. The porous silica monolithic foams with a large pore
size could be fabricated on the centimeter scale from a mixture
of monodispersed PMMA beads or MFI zeolite in the SBA-16
Bull. Korean Chem. Soc. 2015, Vol. 36, 1396–1404
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 1403

BULLETIN OF THE
Article
Application of Mesoporous Silica Foam in Chiral Intermediates Synthesis
KOREAN CHEMICAL SOCIETY
Sheppard, S. B. McCullen, J. B. Higgins, J. L. Schlenker, J.
Am. Chem. Soc. 1992, 114, 10834.
4. O. D. Velev, T. A. Jede, R. F. Lobo, A. M. Lenhoff, Nature 1997,
389, 448.
5. B. T. Holland, C. F. Blanford, A. Stein, Science 1998, 281, 538.
6. A. Imhof, J. Pine, Nature 1997, 389, 948.
7. M. Breulmann, S. A. Davis, S. Mann, H. P. Hentze,
M. Antonietti, Adv. Mater. 2000, 12, 502.
8. D. M. Antonelli, Micropor. Mesopor. Mater. 1999, 33, 209.
9. P. Sepulveda, G. P. Binner, J. Eur. Ceram. Soc. 1999,
19, 2059.
10. S. A. Davis, S. L. Burkett, N. H. Mendelson, S. Mann, Nature
1997, 385, 420.
11. S. H. Kim, C. K. Shin, C. H. Ahn, G.-J. Kim, J. Porous Mater.
2006, 13, 201.
12. (a) A. Stein, Adv. Mater. 2003, 15, 763; (b) M. E. Davis, Nature
2002, 417, 813.
13. J. Aguado, D. P. Serrano, M. D. Romero, J. M. Escola, Chem.
Commun. 1996, 41, 725.
14. A. Corma, M. S. Grande, V. Gonzalez-Alfaro, A. B. Orchilles,
J. Catal. 1996, 159, 375.
15. M. S. Whang, Y. K. Kwon, T. J. Pinnavaia, Science 1995,
269, 1242.
16. G. J. A. Soler-Illia, C. Sanchez, B. Lebeau, J. Patarin, Chem. Rev.
2002, 102, 4093.
17. R. B. Kawthekar, G.-J. Kim, Helv. Chim. Acta 2008, 91, 317.
18. J. M. Ready, E. N. Jacobsen, J. Am. Chem. Soc. 1999, 121, 6086.
19. J. M. Ready, E. N. Jacobsen, J. Am. Chem. Soc. 2001,
123, 2687.
20. R. B. Kawthekar, C. H. Ahn, G.-J. Kim, Catal. Lett. 2007,
115, 62.
21. G.-J. Kim, J. H. Shin, Tetrahedron Lett. 1999, 40, 6827.
22. D. Pini, A. Mandoli, S. Orlandi, P. Salvadori, TetrahedronAsym-
metry 1999, 10, 3883.
silica sol. PMMA or zeolite/SBA silica sol was expanded and
solidified into a foam structure at high temperature. In con-
trast, the dense silica monolith was obtained after full evapo-
ration of the solvent at room temperature without releasing the
foam structure in the monolithic body. After removing the
PMMA polymer beads, the adjacent macropores were inter-
connected through the mesoporous silica walls as an expanded
foam structure. In addition, the micro/meso/macroporous sil-
ica monolith could also be fabricated from the MFI zeolite/
SBA sol mixture by expansion into a foam structure. These
porous supports were used to anchor the (BF3)-containing chi-
ral Co(III) salens, and they were packed in a tube for use as a
catalyst in the continuous flow type packed bed reactor sys-
tem. Based on the asymmetric HKR and PKR reactions, the
chiral Co(III)-(BF3) salen immobilized on the meso/macro
porous silica monolithic foams obtained in the present study
can be applied as effective heterogenized catalysts for those
reactions. The high catalytic properties of meso/ macroporous
materials might expand the number of applications of porous
materials, and can be used in a number of commercial pro-
cesses in the future. Furthermore, such materials with bimodal
meso/macroscopic pores would be useful for many potential
applications, such as heterogeneous catalysts when bulky
reactant molecules are involved.
Acknowledgments.
This research was supported by
Research grant from the National Research Foundation of
Korea (NRF), funded by the Korean Government (MEST)
(No. 3148213322).
References
23. S. B. Ogunwumi, T. Bein, Chem. Commun. 1997, 9, 901.
24. F. Minutolo, D. Pini, P. Salvadori, Tetrahedron Lett. 1996,
37, 3375.
25. Y. Kim, C. Lee, G.-J. Kim, Bull. Korean Chem. Soc. 2010,
31, 2973.
1. A. Corma, Chem. Rev. 1997, 97, 2373.
2. T. E. Gier, X. Bu, P. Feng, G. D. Stucky, Nature 1998, 395, 154.
3. J. S. Beck, J. C. VartUli, W. J. Roth, M. E. Leonowicz, C. T.
Kresge, K. D. Schmitt, C. T.-W. Chu, D. H. Olson, E. W.
Bull. Korean Chem. Soc. 2015, Vol. 36, 1396–1404
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de 1404